A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX

NCT02270632 | Terminated Phase 2

• 1 other identifier: PH-F8IL10-03/13
• Study Type: interventional
• Target: 27
• Locations: 3 countries
• Sites: 8

Brief Summary

A multicenter, randomized, parallel assignment, double blind, placebo-controlled, safety/efficacy phase II study of two different dosages of subcutaneous F8IL10 in patients with active rheumatoid arthritis receiving MTX.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change from baseline in DAS28-CRPscore

  Mean change from baseline in DAS28-CRP between F8IL10 and placebo arms.

  At week 9

Secondary Outcomes (15)

• Number of Participants with Adverse Events

  Up to 8 months from randomization

• Response rate according to ACR and EULAR criteria

  1) week 9; 2) from week 12 up to week 32, every 4 weeks

• Clinical Remission and low-disease activity (DAS28-CRP)

  1) week 9; 2) from week 12 up to week 32, every 4 weeks

• Clinical Remission and low-disease activity (SDAI score)

  1) week 9; 2) from week 12 up to week 32, every 4 weeks

• Absolute count and change from baseline in tender and swollen joint counts

  1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks

Study Arms (3)

Arm 1

PLACEBO COMPARATOR

Placebo

Drug: MTX; Drug: Placebo

Arm 2

EXPERIMENTAL

F8IL10, 30 μg/kg

Drug: F8IL10; Drug: MTX

Arm 3

EXPERIMENTAL

F8IL10, 160 μg/kg

Drug: F8IL10; Drug: MTX

Interventions

F8IL10 DRUG

F8IL10 will be administered once a week for 8 weeks (or until withdrawn from the study).

Also known as: Dekavil

Arm 2; Arm 3

MTX DRUG

All patients enrolled in the study will receive as concomitant therapy MTX at stable dose (10-25 mg/week), and the corresponding fixed dose of folic acid.

Also known as: Methotrexate

Arm 1; Arm 2; Arm 3

Placebo DRUG

Placebo will be administered once a week for 8 weeks (or until withdrawn from the study).

Arm 1

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At the time of enrolment, patients must fulfil all of the following criteria:
• Patients aged ≥18 and \< 75 years.
• Diagnosis of RA according to ACR/EULAR classification criteria (2010) with a disease duration exceeding 6 months.
• Active RA (DAS28 ≥ 3.2) for ≥ 3 months at time of signing informed consent despite MTX therapy (stable regimen of methotrexate 10-25 mg/week orally, subcutaneous or intramuscular injections: stable dosage from ≥ 8 weeks before screening).
• ≥ 6 tender joints out of 68, ≥ 6 swollen joints out of 66 and serum CRP \> 0.5 mg/dl at screening.
• History of inadequate clinical response to at least one anti-TNF drug (applied for at least 3 months).
• Stable regimens of NSAIDs and/or oral corticosteroid (≤ 10 mg/day; prednisone equivalent) for a period ≥ 2 weeks prior to screening.
• All acute toxic effects of any prior therapy must have returned to classification "mild" according to CTCAE v.4.03 (published on June 14, 2010).
• Sufficient hematologic, liver and renal function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥100 x109/L, haemoglobin (Hb) ≥ 10.0 g/dL.
• Alkaline phosphatase (AP), alanine aminotransferase (ALT) and or aspartate aminotransferase (AST) ≤ 3 x upper limit of normal range (ULN), and total bilirubin ≤ 2.0 mg/dl (34.2 µmol/L).
• Creatinine ≤ 1.5 ULN or 24 h creatinine clearance ≥ 50 mL/min.
• Documented negative test for HIV, HBV and HCV. For patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative serum HBV DNA is required.
• All female subjects must have negative pregnancy test results at the screening. Women of childbearing potential must be using simultaneously double-barrier or two acceptable methods of contraception (i.e. intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.) from the screening to three months following the last study drug administration. Pregnancy test will be repeated at the end of treatment visit.
• Male patients must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.

You may not qualify if:

• Patients must not be enrolled into the study if, at the time of enrolment, they have any of the following:
• Presence of active infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or would interfere with the study objectives or conduct.
• Pregnancy, lactation or unwillingness to use adequate contraceptive methods.
• Diagnosis of any other inflammatory arthritis or active autoimmune diseases other than RA.
• Last treatment with monoclonal antibodies (i.e., adalimumab, infliximab, golimumab, tocilizumab, certolizumab pegol) less than 8 weeks prior to first administration of study drugs. Last treatment with rituximab less than 16 weeks prior to first administration of study drugs. Last treatment with fusion proteins (i.e., abatacept, etanercept) less than 4 weeks prior to first administration of study drugs.
• Treatment with any immunosuppressant drug other than MTX and corticosteroids.
• Active or latent tuberculosis (TB).
• HIV infection.
• Acute or chronic HBV or HCV infection, as assessed by serology or serum HBV DNA.
• History or currently active primary or secondary immunodeficiency.
• Concurrent malignancy or history of malignancy from which the patient has been disease-free for less than 5 years.
• History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Treatment with warfarin or other coumarin derivatives.
• Heart insufficiency (\> Grade II, NYHA criteria).
• Irreversible cardiac arrhythmias requiring permanent medication.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (8)

Universitatsklinikum Essen

Essen, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Schön Klinik Hamburg Eilbek

Hamburg, Germany

Location

Ospedale Luigi Sacco, Milano

Milan, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Italy

Location

HFR Fribourg - Hôpital Cantonal

Fribourg, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 21, 2014
• Study Start: October 1, 2014
• Primary Completion: April 1, 2019
• Study Completion: June 8, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

DE (3); CH (2); IT (3)